This project studies the physiology and pharmacology of excitatory amino acid receptors and their role in synaptic transmission in dissociated cultures of mouse spinal cord. Three receptor types exist: kainate, quisqualate and N-methyl-D-aspartate (NMDA). Magnesium ions cause a voltage-dependent block of the ion channels linked to NMDA receptors. Major new discoveries in the project were selectivity of the divalent cation binding site linked to the NMDA receptor ion channel. Two potent calcium channel blockers, nickel (Ni++) and cadmium (Ca++) ions, have strikingly different cations on responses to NMDA, Ni++ being a strong antagonist and Cd++ nearly ineffective. Reversal potential measurements suggest that calcium ions permeate through NMDA ion channels. Extreme membrane potential hyperpolarization may also force magnesium ions past the blocking site. Excitatory synaptic transmission in spinal cord cultures appears to result from activation of non-NMDA receptor types. The non-selective antagonist cis-2,3-piperidine dicarboxylic acid (PDA) reversibly blocked epsps while the selective NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) was ineffective. The excitatory synaptic current decayed as a single exponential of time constant 0.5 - 1.0 msec. The decay time constant was voltage insensitive between -80 and 0 mV, and the peak current voltage relation was linear.